Background
IgG4-related disease is a chronic, immune-mediated fibroinflammatory condition affecting multiple organs. Current treatments, primarily glucocorticoids, are associated with high toxicity and frequent disease flares upon discontinuation. Obexelimab, a bifunctional, non-cytolytic, humanised monoclonal antibody, targets CD19 and Fc gamma receptor IIb to inhibit B cells, plasmablasts, and CD19-expressing plasma cells, offering a novel therapeutic approach.
Methods
An open-label, single-arm, phase 2 pilot trial was conducted at Massachusetts General Hospital, involving 15 patients aged 18-80 with active IgG4-related disease. Patients received 5 mg/kg of obexelimab intravenously every 2 weeks for 24 weeks. The primary endpoint was a decrease of 2 or more in the IgG4-related disease responder index at day 169.
Findings
12 out of 15 patients achieved the primary endpoint, with 14 considered responders. Significant reductions in serum B cells and plasmablasts were observed, although B cells recovered to 75% of baseline within 42 days post-treatment. Adverse events were reported in 13 patients, with one leading to treatment discontinuation.
Interpretation
The trial suggests obexelimab leads to clinical improvement in IgG4-related disease, with most patients achieving complete remission without glucocorticoids. The reversible inhibition of B-cell function without prolonged depletion supports further development of obexelimab as a treatment for IgG4-related disease and potentially other B-cell-mediated autoimmune conditions.
Funding
The study was supported by Xencor, Zenas BioPharma, and the National Institutes of Health.
